St. Jude Children's Research Hospital

About: St. Jude Children's Research Hospital is a healthcare organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Virus. The organization has 9344 authors who have published 19233 publications receiving 1233399 citations. The organization is also known as: St. Jude Children's Hospital & St. Jude Hospital.

Germline Genetic Variation in an Organic Anion Transporter Polypeptide Associated With Methotrexate Pharmacokinetics and Clinical Effects

Abstract: Purpose Methotrexate plasma concentration is related to its clinical effects. Our aim was to identify the genetic basis of interindividual variability in methotrexate pharmacokinetics in children with newly diagnosed acute lymphoblastic leukemia (ALL). Patients and Methods We performed a genome-wide analysis of 500,568 germline single-nucleotide polymorphisms (SNPs) to identify how inheritance affects methotrexate plasma disposition among 434 children with ALL who received 3,014 courses of methotrexate at 2 to 5 g/m2. SNPs were validated in an independent cohort of 206 patients. Results Adjusting for age, race, sex, and methotrexate regimen, the most significant associations were with SNPs in the organic anion transporter polypeptide, SLCO1B1. Two SNPs in SLCO1B1, rs11045879 (P = 1.7 × 10−10) and rs4149081 (P = 1.7 × 10−9), were in linkage disequilibrium (LD) with each other (r2 = 1) and with a functional polymorphism in SLCO1B1, T521C (rs4149056; r2 > 0.84). rs11045879 and rs4149081 were validated in an ...

Paediatric cancer in low-income and middle-income countries

Abstract: Summary Patterns of cancer incidence across the world have undergone substantial changes as a result of industrialisation and economic development. However, the economies of most countries remain at an early or intermediate stage of development—these stages are characterised by poverty, too few health-care providers, weak health systems, and poor access to education, modern technology, and health care because of scattered rural populations. Low-income and middle-income countries also have younger populations and therefore a larger proportion of children with cancer than high-income countries. Most of these children die from the disease. Chronic infections, which remain the most common causes of disease-related death in all except high-income countries, can also be major risk factors for childhood cancer in poorer regions. We discuss childhood cancer in relation to global development and propose strategies that could result in improved survival. Education of the public, more and better-trained health professionals, strengthened cancer services, locally relevant research, regional hospital networks, international collaboration, and health insurance are all essential components of an enhanced model of care.

The LPS receptor (CD14) links innate immunity with Alzheimer's disease.

Abstract: SPECIFIC AIMIn Alzheimer’s disease (AD), chronic neuroinflammation induced by amyloid peptide (Aβ) fibrils is considered to contribute to progressive neurodegeneration. We studied whether the LPS receptor (CD14), crucial in cellular activation by highly hydrophobic and aggregated microbial components, mediates inflammatory activation by hydrophobic aggregated Aβ and whether this key innate immunity receptor is associated with pathological features in a mouse model of AD.PRINCIPAL FINDINGS1. CD14 interacts with Aβ fibrilsTo determine whether CD14 binds Alzheimer Aβ, we coincubated fibrillar human Aβ(1-42) with recombinant soluble murine CD14. Complexes were immunoprecipitated and assessed by Western blot. The results demonstrate binding of Aβ fibrils to CD14. Omission of Aβ or use of an isotype control antibody prevented the precipitation of CD14. Coincubation with the control peptide TNF-α receptor II instead of CD14 did not result in a coimmunoprecipitation as indicated by the absence of a corresponding ...

The clinical pharmacogenomics implementation consortium: CPIC guideline for SLCO1B1 and simvastatin-induced myopathy

Abstract: Cholesterol reduction from statin therapy has been one of the greatest public health successes in modern medicine. Simvastatin is among the most commonly used prescription medications. A non-synonymous coding single-nucleotide polymorphism (SNP), rs4149056, in SLCO1B1 markedly increases systemic exposure to simvastatin and the risk of muscle toxicity. This guideline explores the relationship between rs4149056 (c.521T>C, p.V174A) and clinical outcome for all statins. The strength of the evidence is high for myopathy with simvastatin. We limit our recommendations accordingly.